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1.
Open Heart ; 7(2)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33154144

RESUMO

OBJECTIVE: The association between the use of renin-angiotensin-aldosterone (RAAS) inhibitors and the risk of mortality from COVID-19 is unclear. We aimed to estimate the association of RAAS inhibitors, including ACE inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) with COVID-19 mortality risk in patients with hypertension. METHODS: PubMed (MEDLINE) SCOPUS, OVID, Cochrane Library databases and medrxiv.org were searched from 1 January 2020 to 1 September 2020. Studies reporting the association of RAAS inhibitors (ACEi or ARBs) and mortality in patients with hypertension, hospitalised for COVID-19 were extracted. Two reviewers independently extracted appropriate data of interest and assessed the risk of bias. All analyses were performed using random-effects models on log-transformed risk ratio (RR) estimates, and heterogeneity was quantified. RESULTS: Fourteen studies were included in the systematic review (n=73,073 patients with COVID-19; mean age 61 years; 53% male). Overall, the between-study heterogeneity was high (I2=80%, p<0.01). Patients with hypertension with prior use of RAAS inhibitors were 35% less likely to die from COVID-19 compared with patients with hypertension not taking RAAS inhibitors (pooled RR 0.65, 95% CI 0.45 to 0.94). The quality of evidence by Grading of Recommendations, Assessment, Development and Evaluations was graded as 'moderate' quality. CONCLUSIONS: In this meta-analysis, with prior use of RAAS inhibitors was associated with lower risk mortality from COVID-19 in patients with hypertension. Our findings suggest a potential protective effect of RAAS-inhibitors in COVID-19 patients with hypertension. PROSPERO REGISTRATION NUMBER: The present study has been registered with PROSPERO (registration ID: CRD 42020187963).


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Infecções por Coronavirus/mortalidade , Hospitalização , Hipertensão/tratamento farmacológico , Pneumonia Viral/mortalidade , Sistema Renina-Angiotensina/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/mortalidade , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Fatores de Proteção , Medição de Risco , Fatores de Risco , Resultado do Tratamento
2.
J Renin Angiotensin Aldosterone Syst ; 21(4): 1470320320972018, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33169644

RESUMO

In the wake of the COVID-19 pandemic it has become clear that there is a need for therapies that are capable of reducing damage caused to patients from infections. Infections that induce Acute Respiratory Distress Syndrome (ARDS) are especially devastating because lung damage is so critical and difficult to manage. Angiotensin (1-7) [A(1-7)] has already been shown to protect pulmonary health and architecture in various models of disease. There is also evidence that A(1-7) can modulate immune function and protect various organs (lung, kidney, and heart) from oxidative damage and inflammation. Here we focus on making a case for the development of novel therapies that target the protective arm of the Renin Angiotensin System (RAS).


Assuntos
Angiotensina I/uso terapêutico , Betacoronavirus/fisiologia , Infecções por Coronavirus/complicações , Fragmentos de Peptídeos/uso terapêutico , Pneumonia Viral/complicações , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/virologia , Angiotensina I/fisiologia , Animais , Infecções por Coronavirus/mortalidade , Humanos , Pandemias , Fragmentos de Peptídeos/fisiologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/mortalidade , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia
3.
J Diabetes Res ; 2020: 8205261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134395

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic continues to cause havoc to many countries of the globe, with no end in sight, due to nonavailability of a given vaccine or treatment regimen. The pandemic has so far had a relatively limited impact on the African continent, which contributes more than 93% of global malaria burden. However, the limited burden of COVID-19 pandemic on the African region could have long-term implications on the health and wellbeing of affected inhabitants due to its malaria-endemic status. Malaria causes recurrent insulin resistance with episodes of infection at relatively low parasitaemia. Angiotensin-converting enzyme 2 (ACE2) which is widely distributed in the human body is implicated in the pathogenesis of malaria, type 2 diabetes mellitus (T2DM), and COVID-19. Use of ACE2 by the COVID-19 virus induces inflammation and oxidative stress, which can lead to insulin resistance. Although COVID-19 patients in malaria-endemic African region may not exhibit severe signs and symptoms of the disease, their risk of exhibiting heightened insulin resistance and possible future development of T2DM is high due to their prior exposure to malaria. African governments must double efforts at containing the continued spread of the virus without neglecting existing malarial control measures if the region is to avert the plausible long-term impact of the pandemic in terms of future development of T2DM.


Assuntos
Infecções por Coronavirus/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/patologia , Doenças Endêmicas , Malária/epidemiologia , Pneumonia Viral/epidemiologia , África/epidemiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus/fisiologia , Infecções por Coronavirus/complicações , Diabetes Mellitus Tipo 2/complicações , Progressão da Doença , Humanos , Resistência à Insulina/fisiologia , Malária/complicações , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/patologia , Estado Pré-Diabético/virologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia
4.
Geriatr Psychol Neuropsychiatr Vieil ; 18(2): 141-148, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33064080

RESUMO

Coronavirus disease 2019 (COVID-19) is a secondary infectious disease caused by severe acute respiratory syndrome coronavirus 2. The link between cardiovascular disease and COVID-19 appears to be twofold. First, some reports indicate that certain groups of patients are at greater risk of COVID-19, including patients with cardiovascular risk factors, pre-existing cardiovascular conditions and older patients. In addition, the outcomes these patients face are disproportionately more severe. Second, SARS-CoV-2 infection can be complicated by life-threatening acute cardiovascular diseases. Despite the rapid ongoing evolution of information about this pandemic, this review aims to highlight cardiovascular pathologies related to COVID-19 as either comorbidities, including concerns and uncertainty regarding the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on angiotensin conversion enzyme 2, or cardiovascular complications.


Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/terapia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Comorbidade , Humanos , Pandemias , Peptidil Dipeptidase A/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos
5.
Drugs Aging ; 37(11): 779-785, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33084001

RESUMO

This paper presents a brief overview of the complex interaction between age, hypertension, the renin-angiotensin-aldosterone system (RAAS), inflammation, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. Coronavirus disease 2019 (COVID-19) is more frequent and more severe in comorbid elderly patients, especially those with hypertension, diabetes, obesity, or cardiovascular diseases. There are concerns regarding the use of RAAS inhibitors in patients with COVID-19. Some physicians have considered the need for interrupting RAAS inhibition in order to reduce the possibility of SARS-CoV2 entering lung cells after binding to angiotensin-converting enzyme 2 (ACE2) receptors. We offer a different point of view in relation to the need for continuing to use RAAS inhibitors in patients with COVID-19. We focused our article on elderly patients because of the distinctive imbalance between the immune response, which is depressed, and the exacerbated inflammatory response, 'inflammaging', which makes the geriatric patient an appropriate candidate for therapeutic strategies aimed at modulating the inflammatory response. Indeed, COVID-19 is an inflammatory storm that starts and worsens during the course of the disease. During the COVID-19 pandemic, various therapeutic approaches have been tested, including antiviral drugs, interferon, anti-interleukins, hydroxychloroquine, anti-inflammatories, immunoglobulins from recovered patients, and heparins. Some of these therapeutic approaches did not prove to be beneficial, or even induced serious complications. Based on current evidence, in the early stages of the disease modulation of the inflammatory response through the inhibition of neprilysin and modulation of the RAAS could affect the course and outcome of COVID-19.


Assuntos
Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Betacoronavirus , Infecções por Coronavirus , Hipertensão/tratamento farmacológico , Inflamação , Pandemias , Pneumonia Viral , Idoso , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/imunologia , Humanos , Fatores Imunológicos/farmacologia , Inflamação/tratamento farmacológico , Inflamação/imunologia , Neprilisina/antagonistas & inibidores , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Sistema Renina-Angiotensina/efeitos dos fármacos
6.
Bol Med Hosp Infant Mex ; 77(5): 274-281, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33064690

RESUMO

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients with hypertension and other cardiovascular comorbidities develop more severe coronavirus disease (COVID)-19 and are at high risk of death, a controversy arose about the use of antihypertensives as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs). Such drugs might increase the expression of the fundamental receptor of this new infectious agent: the angiotensin-converting enzyme 2 (ACE2). Preclinical observations indicate that the increase of ACE2 expression or the activity by ACEis and ARBs leads to a greater transformation of angiotensin (Ang)-II to Ang-(1-7), which is associated with positive effects on cardiovascular and pulmonary pathophysiology. This association has been demonstrated in observational studies in patients with cardiovascular pathology and pneumonia. It has not been possible to confirm whether users of ACEis or ARBs are more infected by the new coronavirus, due to methodological issues in studies with patients infected with SARS-CoV-2. However, the use of such antihypertensive treatments in both children and adults might reduce the virulence of infection. Therefore, changes in the antihypertensive therapy of patients at risk of contracting COVID-19 are not recommended.


Assuntos
Anti-Hipertensivos/administração & dosagem , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Adulto , Antagonistas de Receptores de Angiotensina/administração & dosagem , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Criança , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Humanos , Hipertensão/tratamento farmacológico , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/mortalidade , Sistema Renina-Angiotensina/efeitos dos fármacos , Fatores de Risco
8.
J Pharmacol Sci ; 144(4): 218-228, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33070841

RESUMO

Myocardial ischemia initiates a chain of pathological conditions leading to cardiomyocyte death. Therefore, pharmacological treatment to stop ischemia-induced damage is necessary. Fibrates, have been reported to decrease inflammatory markers and to modulate the renin-angiotensin system (RAS). Our aim was to explore if clofibrate treatment, administered one week after myocardial event, decreases MI-induced cardiac damage. Wistar rats were assigned to: 1. Sham or 2. Coronary artery ligation (MI). Seven days after, rats were subdivided to receive vehicle (V) or clofibrate [100 mg/kg (C)] daily for 7 days. Blood samples and left ventricle were analyzed. RAS components [angiotensin II, angiotensin converting enzyme (ACE), and AT1-receptor] decreased in MI-C compared to MI-V, while [Ang-(1-7), bradykinin, ACE-2, and AT2-receptor] raised in response to clofibrate treatment. Oxidative stress markers increased in MI-V rats, a profile reverted in MI-C rats. Nitric oxide (NO) pathway (Akt, eNOS, and NO) exhibits a lower participation in MI-V, but clofibrate raised NO-pathway components and its production. MI-induced fibrosis and structural damage was also improved by clofibrate-treatment. In conclusion, clofibrate administration to 7 days MI-rats exerts an antioxidant, pro-vasodilator expression profile, and anti-fibrotic effect suggesting that PPARα activation can be considered a therapeutic target to improve cardiac condition posterior to ischemia.


Assuntos
Clofibrato/administração & dosagem , Clofibrato/farmacologia , Ventrículos do Coração/metabolismo , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/metabolismo , Miocárdio/patologia , Óxido Nítrico/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Angiotensina II/metabolismo , Animais , Fibrose , Ventrículos do Coração/patologia , Masculino , Isquemia Miocárdica/patologia , Estresse Oxidativo/efeitos dos fármacos , Peptidil Dipeptidase A/metabolismo , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismo , Fatores de Tempo
9.
J Am Heart Assoc ; 9(19): e017297, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-32998607

RESUMO

Background Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) may worsen the prognosis of coronavirus disease 2019, but any association could be confounded by the cardiometabolic conditions indicating ACE-I/ARB use. We therefore examined the impact of ACE-Is/ARBs on respiratory tract infection outcomes. Methods and Results This cohort study included all adult patients hospitalized with influenza or pneumonia from 2005 to 2018 in Denmark using population-based medical databases. Thirty-day mortality and risk of admission to the intensive care unit in ACE-Is/ARBs users was compared with nonusers and with users of calcium channel blockers. We used propensity scores to handle confounding and computed propensity score-weighted risks, risk differences (RDs), and risk ratios (RRs). Of 568 019 patients hospitalized with influenza or pneumonia, 100 278 were ACE-I/ARB users and 37 961 were users of calcium channel blockers. In propensity score-weighted analyses, ACE-I/ARB users had marginally lower 30-day mortality than users of calcium channel blockers (13.9% versus 14.5%; RD, -0.6%; 95% CI, -1.0 to -0.1; RR, 0.96; 95% CI, 0.93-0.99), and a lower risk of admission to the intensive care unit (8.0% versus 9.6%; RD, -1.6%; 95% CI, -2.0 to -1.2; RR, 0.83; 95% CI, 0.80-0.87). Compared with nonusers, current ACE-I/ARB users had lower mortality (RD, -2.4%; 95% CI, -2.8 to -2.0; RR, 0.85; 95% CI, 0.83-0.87), but similar risk of admission to the intensive care unit (RD, 0.4%; 95% CI, 0.0-0.7; RR, 1.04; 95% CI, 1.00-1.09). Conclusions Among patients with influenza or pneumonia, ACE-I/ARB users had no increased risk of admission to the intensive care unit and slightly reduced mortality after controlling for confounding.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Pneumonia/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Influenza Humana/epidemiologia , Masculino , Razão de Chances , Pandemias , Pneumonia/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida/tendências
10.
Intern Med ; 59(18): 2237-2244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32938851

RESUMO

Objective The intrarenal renin-angiotensin system (RAS) is activated in chronic kidney disease (CKD) patients and is not suppressed at night in CKD patients showing nocturnal hypertension, contributing to renal damage. Furthermore, changes in RAS inhibitor administration from morning to evening, namely chronotherapy, ameliorates renal damage at night. We attempted to clarify whether or not chronotherapy ameliorates renal damage by suppressing the intrarenal RAS activity. Methods We recruited 34 CKD patients with RAS inhibitors in the morning. We conducted ambulatory blood pressure (BP) monitoring and urine collection and evaluated urinary albumin (Alb) and angiotensinogen (AGT), which are surrogate markers for intrarenal RAS activity during the day and at night, respectively. The same experiments were conducted after changing the administration time. The ratio of values associated with morning versus evening dosing was defined as the morning to evening (M/E) ratio. Results The M/E ratio of urinary Alb had a significant and positive relationship with that of urinary AGT during the day and at night in all CKD patients. However, no significant relationships were found between the M/E ratios of urinary Alb and AGT using multiple linear regression analyses. Conversely, there was a significant and positive relationship between the M/E ratios of urinary Alb and AGT at night but not during the day in CKD patients whose estimated glomerular filtration rate was <45 mL/min/1.73 m2 and whose night-to-day ratio of systolic BP was >0.90, even after adjustment. Conclusion This study indicated that chronotherapy with RAS inhibitors improved the renal damage via intrarenal RAS suppression, especially in CKD patients with an impaired renal function and nocturnal hypertension.


Assuntos
Cronoterapia Farmacológica , Rim/fisiopatologia , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Adulto , Albuminúria , Angiotensinogênio/urina , Biomarcadores/sangue , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Insuficiência Renal/complicações , Sistema Renina-Angiotensina/fisiologia
12.
Hipertens. riesgo vasc ; 37(3): 101-107, jul.-sept. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-193518

RESUMO

INTRODUCTION: Blood pressure (BP) control is fundamental to the care of patients with chronic kidney disease (CKD), and is relevant at all stages of CKD. Renin-angiotensin-aldosterone system (RAAS) blockers have shown to be effective, not only in BP control but also in reducing proteinuria and slowing CKD progression. However, there is a lack of evidence for recommending RAAS blockers in elderly patients with CKD without proteinuria. The primary outcome of the present study is to evaluate the impact of RAAS blockers on CKD progression in elderly patients without proteinuria. MATERIALS AND METHODS: The PROERCAN trial (trial registration, NCT03195023) is a multicentre open-label, randomized controlled clinical trial with 110 participants over 65 years-old with hypertension and CKD stages 3-4 without proteinuria. Patients will be randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs, and will be followed up for three years. Primary outcome is the estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcomes include BP control, renal and cardiovascular events, and mortality. RESULTS AND CONCLUSIONS: The design of this trial is presented here. The results will show if antihypertensive treatment with RAAS blockers has an impact on CKD progression in elderly patients without proteinuria. Any differences in BP control, cardiovascular events, and mortality with each antihypertensive treatment will be also clarified


INTRODUCCIÓN: El control de la presión arterial (PA) es fundamental para los pacientes con enfermedad renal crónica (ERC) y es relevante en todos los estadios de ERC. Los bloqueantes del sistema renina-angiotensina-aldosterona (BSRAA) han demostrado su efectividad no solo en el control de la PA sino también en la reducción de la proteinuria y de la progresión de la ERC. Sin embargo, no existe evidencia para recomendar el uso de BSRAA en pacientes añosos con ERC sin proteinuria. El objetivo principal del estudio es evaluar el impacto de los BSRAA en la progresión de ERC en pacientes añosos sin proteinuria. MATERIAL Y MÉTODOS: El estudio PROERCAN (NCT03195023) es un ensayo clínico multicéntrico, abierto, aleatorizado de 110 pacientes hipertensos, mayores de 65 años con ERC estadios3 y4 sin proteinuria. Los pacientes son aleatorizados 1:1 a recibir tratamiento con BSRAA u otros antihipertensivos y el seguimiento será de 3años. La variable principal es el descenso del filtrado glomerular estimado durante el tiempo de seguimiento. Las variables secundarias incluyen las cifras de PA, eventos renales y cardiovasculares y mortalidad. RESULTADOS Y CONCLUSIÓN: El diseño del ensayo clínico se desarrolla en el presente artículo. Los resultados determinarán si el tratamiento antihipertensivo con BSRAA tiene un impacto en la progresión de la ERC en pacientes añosos sin proteinuria. Así mismo, se aclararán las diferencias en el control de la PA, los eventos cardiovasculares y la mortalidad con los distintos tratamientos antihipertensivos


Assuntos
Humanos , Idoso , Idoso de 80 Anos ou mais , Sistema Renina-Angiotensina/efeitos dos fármacos , Insuficiência Renal Crônica/terapia , Proteinúria/etiologia , Progressão da Doença , Proteinúria/terapia , Taxa de Filtração Glomerular
13.
Drug Discov Ther ; 14(4): 161-170, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908071

RESUMO

Coronavirus disease 2019 (COVID-19) is found to be associated with various comorbidities which include cardiovascular diseases, hypertension, and diabetes. The impaired regulation of renin-angiotensin-aldosterone system (RAAS) has been seen in COVID-19 patients, but whether RAAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are responsible for worsening of clinical conditions remains unknown. Herein, we review the role of angiotensin-converting enzyme 2 (ACE2) expression in disease progression, its association with comorbidities and COVID-19, and summarize the clinical evidence for several potential directions for future research work on ACEIs/ARBs in COVID-19 patients.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/virologia , Sistema Renina-Angiotensina , Internalização do Vírus , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/enzimologia , Interações entre Hospedeiro e Microrganismos , Humanos , Pandemias , Segurança do Paciente , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/enzimologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Internalização do Vírus/efeitos dos fármacos
14.
Ecotoxicol Environ Saf ; 203: 111044, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888613

RESUMO

BACKGROUND: Exposure to ambient fine particulate matter (PM2.5) is associated with various adverse health outcomes. Although several mechanisms have been proposed including oxidative stress and inflammatory responses, the exact mechanism is still unknown. Few studies have investigated the mechanism linking PM2.5 and blood pressure (BP). In this study, we measured urinary metabolites and BP -related renin-angiotensin-aldosterone system (RAAS) to investigate the associations between ambient PM2.5 exposure and BP in healthy C57BL/6 mice. METHODS: The C57BL/6 mice were exposed to ambient concentrated PM2.5 or filtered air (FA) for 16 weeks. Systolic BP and diastolic BP were measured by noninvasive BP system. The urine metabolites were quantified using the untargeted metabolomics approach. The expression of RAAS-related proteins angiotensin-converting enzyme (ACE)2, angiotensin (Ang) II, Ang (1-7) and aldosterone (ALD) were measured using Western blot and ELISA kits. RESULTS: The metabolomics analysis demonstrated that PM2.5 exposure induced significant changes of some metabolites in urine, including stress hormones, amino acids, fatty acids, and lipids. Furthermore, there was an elevation of BP, increase of serous Ang II and ALD, along with the decrease of ACE2 and Ang (1-7) in kidney in the PM2.5-exposed mice compared with FA-exposed mice. CONCLUSIONS: The results demonstrated that PM2.5 exposure-induced BP elevation might be associated with RAAS activation. Meanwhile, PM2.5 exposure-induced changes of stress hormone and lipid metabolism might mediate the activation of RAAS. The results suggested that the systemic stress hormone and lipid metabolism was associated with the development of hypertension.


Assuntos
Poluentes Atmosféricos/toxicidade , Angiotensina I/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/induzido quimicamente , Material Particulado/toxicidade , Fragmentos de Peptídeos/metabolismo , Peptidil Dipeptidase A/metabolismo , Acetilglucosaminidase/urina , Angiotensina I/sangue , Animais , Biomarcadores/sangue , Biomarcadores/urina , Hipertensão/urina , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Metaboloma/efeitos dos fármacos , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos/sangue , Peptidil Dipeptidase A/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , beta-Galactosidase/urina
15.
Hypertension ; 76(5): 1563-1571, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32869673

RESUMO

The viral spike coat protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engages the human ACE (angiotensin-converting enzyme) 2 cell surface receptor to infect the host cells. Thus, concerns arose regarding theoretically higher risk for coronavirus disease-19 (COVID-19) in patients taking ACE inhibitors/angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]). We systematically assessed case-population and cohort studies from MEDLINE (Ovid), Cochrane Database of Systematic Reviews PubMed, Embase, medRXIV, the World Health Organization database of COVID-19 publications, and ClinicalTrials.gov through June 1, 2020, with planned ongoing surveillance. We rated the certainty of evidence according to Cochrane methods and the Grading of Recommendations Assessment, Development and Evaluation approach. After pooling the adjusted odds ratios from the included studies, no significant increase was noted in the risk of SARS-CoV-2 infection by the use of ACE inhibitors (adjusted odds ratio, 0.95 [95% CI, 0.86-1.05]) or ARBs (adjusted odds ratio, 1.05 [95% CI, 0.97-1.14]). However, the random-effects meta-regression revealed that age may modify the SARS-CoV-2 infection risk in subjects with the use of ARBs (coefficient, -0.006 [95% CI, -0.016 to 0.004]), that is, the use of ARBs, as opposed to ACE inhibitors, specifically augmented the risk of SARS-CoV-2 infection in younger subjects (<60 years old). The use of ACE inhibitors might not increase the susceptibility of SARS-CoV-2 infection, severity of disease, and mortality in case-population and cohort studies. Additionally, we discovered for the first time that the use of ARBs, as opposed to ACE inhibitors, specifically augmented the risk of SARS-CoV-2 infection in younger subjects, without obvious effects on COVID-19 outcomes.


Assuntos
Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Hipertensão/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Síndrome Respiratória Aguda Grave/induzido quimicamente , Síndrome Respiratória Aguda Grave/epidemiologia , Idoso , Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Causas de Morte , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Medição de Risco , Análise de Sobrevida
16.
PLoS One ; 15(9): e0239100, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32925953

RESUMO

OBJECTIVE: This observational study aimed to examine the prognostic association of angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin receptor blockers (ARB) in different left ventricular ejection fraction (LVEF) categories. METHODS: In 3717 patients enrolled in the KCHF Registry, a multicentre registry including consecutive patients hospitalized for acute heart failure (HF), we assessed patient characteristics and association between ACE-I/ARB and clinical outcomes according to LVEF. In the three LVEF categories (reduced LVEF [HFrEF], mid-range LVEF [HFmrEF] and preserved LVEF [HFpEF]), we compared the patients with ACE-I/ARB as discharge medication and those without, and assessed their 1-year clinical outcomes. We defined the primary outcome measure as a composite of all-cause death and HF hospitalization. RESULTS: The 1-year cumulative incidences of the primary outcome measure were 36.3% in HFrEF, 30.1% in HFmrEF and 33.8% in HFpEF (log-rank P = 0.07). The adjusted risks of the ACE-I/ARB group relative to the no ACE-I/ARB group for the primary outcome measure were significantly lower in HFrEF and HFmrEF (HR 0.66 [95%CI 0.54-0.79], P<0.001, and HR 0.61 [0.45-0.82], P = 0.001, respectively), but not in HFpEF (HR 0.95 [0.80-1.14], P = 0.61). There was a significant interaction between the LVEF category and the ACE-I/ARB use on the primary outcome measure (Pinteraction = 0.01). CONCLUSIONS: ACE-I/ARB for patients who were hospitalized for acute HF was associated with significantly lower risk for a composite of all-cause death and HF hospitalization in HFrEF and HFmrEF, but not in HFpEF. ACE-I/ARB might be a potential treatment option in HFmrEF as in HFrEF.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Função Ventricular Esquerda/fisiologia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Causas de Morte , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , Japão/epidemiologia , Masculino , Prognóstico , Sistema de Registros/estatística & dados numéricos , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/fisiologia , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos
17.
Ann Intern Med ; 173(6): JC35, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32926815

RESUMO

SOURCE CITATION: Reynolds HR, Adhikari S, Pulgarin C, et al. Renin-angiotensin-aldosterone system inhibitors and risk of Covid-19. N Engl J Med. 2020;382:2441-8. 32356628.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos , Betacoronavirus , Humanos , Sistema Renina-Angiotensina/efeitos dos fármacos
18.
Arch Cardiovasc Dis ; 113(8-9): 572-578, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32863157

RESUMO

Severe acute respiratory syndrome coronavirus 2, which is responsible for the current coronavirus disease 2019 pandemic, uses angiotensin-converting enzyme 2 as a gateway into host cells. In this review, we summarise the biology of this enzyme, which plays a key role in cardiovascular homeostasis. Blockers of the renin-angiotensin system modify the expression and activity of angiotensin-converting enzyme 2 in different ways. The effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the expression and enzyme activity of angiotensin-converting enzyme 2 are reviewed, and the consequences of these treatments for the severity of coronavirus disease 2019 infection are discussed.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pandemias , Pneumonia Viral/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Humanos , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo
19.
Cardiovasc Ther ; 2020: 4349612, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983258

RESUMO

Background: Central aortic blood pressure (CABP) indices, central hemodynamics, and arterial stiffness are better predictors of cardiovascular events as compared with brachial cuff pressure measurements alone. The present study is aimed at assessing the effects of different antihypertensive drug combination regimens involving renin-angiotensin-aldosterone system (RAAS) inhibitors on CABP indices in Indian patients with hypertension. Methods: This was a cross-sectional, single-center study conducted in patients treated for hypertension for >6 weeks using different treatment regimens involving the combination of RAAS inhibitors with drugs from other classes. CABP indices, vascular age, arterial stiffness, and central hemodynamics were measured in patients using the noninvasive Agedio B900 device (IEM, Stolberg, Germany) and compared between different treatment regimens. Results: A total of 199 patients with a mean age of 54.22 ± 10.15 years were enrolled, where 68.8% had hypertension for over three years and 50.25% had their systolic blood pressure (SBP) < 140 mmHg. Combination treatment with angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) was given to 77.9% and to 20.1% patients, respectively. The mean vascular age was higher than the actual age (58.13 ± 12.43 vs. 54.22 ± 10.15, p = 0.001). The SBP and diastolic blood pressure (DBP) levels in patients treated with ACEI-based combinations were lower than those in patients treated with ARB-based combinations (p < 0.05). The mean central pulse pressure amplification, augmentation pressure, and augmentation index were lower in patients treated with ACEI-based combinations than those treated with other treatments (p = 0.001). In a subgroup analysis, patients given perindopril and calcium channel blockers (CCBs) or diuretics had significantly lower CABP and pulse wave velocity than those given other treatments (p < 0.05). A total of 6.5% patients experienced any side effects. Conclusion: The majority of central hemodynamic parameters, including vascular age, were found to improve more effectively in patients treated with ACEIs than with ARBs. Our results indicate a gap between routine clinical practice and evidence-based guidelines in Indian settings and identify a need to reevaluate the current antihypertensive prescription strategy.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Arterial/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Estudos Transversais , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Índia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
20.
Clin Sci (Lond) ; 134(18): 2489-2501, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32990314

RESUMO

Angiotensin-converting enzyme (ACE) is a zinc membrane metallopeptidase that plays a key role in regulating vasoactive peptide levels and hence cardiovascular activity through its conversion of angiotensin I (Ang I) to Ang II and its metabolism of bradykinin. The discovery of its homologue, ACE2, 20 years ago has led to intensive comparisons of these two enzymes revealing surprising structural, catalytic and functional distinctions between them. ACE2 plays multiple roles not only as a vasopeptidase but also as a regulator of amino acid transport and serendipitously as a viral receptor, mediating the cellular entry of the coronaviruses causing severe acute respiratory syndrome (SARS) and, very recently, COVID-19. Catalytically, ACE2 functions as a monocarboxypeptidase principally converting the vasoconstrictor angiotensin II to the vasodilatory peptide Ang-(1-7) thereby counterbalancing the action of ACE on the renin-angiotensin system (RAS) and providing a cardioprotective role. Unlike ACE, ACE2 does not metabolise bradykinin nor is it inhibited by classical ACE inhibitors. However, it does convert a number of other regulatory peptides in vitro and in vivo. Interest in ACE2 biology and its potential as a possible therapeutic target has surged in recent months as the COVID-19 pandemic rages worldwide. This review highlights the surprising discoveries of ACE2 biology during the last 20 years, its distinctions from classical ACE and the therapeutic opportunities arising from its multiple biological roles.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Angiotensina II/efeitos dos fármacos , Angiotensina II/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Infecções por Coronavirus/metabolismo , Humanos , Pandemias , Pneumonia Viral/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia , Vasoconstritores/farmacologia
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